Study to Assess Safety of HDP-101 in Patients With Relapsed Refractory Multiple Myeloma

• ClinicalTrials.gov Identifier: NCT04879043
• Recruitment Status: Recruiting
• First Posted: May 10, 2021
• Last Update Posted: July 14, 2023
• Sponsor: Heidelberg Pharma AG
• Information provided by (Responsible Party): Heidelberg Pharma AG

Tracking Information

• First Submitted Date: April 23, 2021
• First Posted Date: May 10, 2021
• Last Update Posted Date: July 14, 2023
• Actual Study Start Date: February 7, 2022
• Estimated Primary Completion Date: August 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 4, 2021)

• Number of patients who experience dose-limiting toxicity (DLT) during the first cycle of treatment - Part 1 as defined in Clinical Study Protocol [ Time Frame: Up to Day 21 (from first dose) ]
• Objective response rate (ORR) [ Time Frame: Through study completion, an average of 1 year ]
  Proportion of enrolled subjects who achieve a partial response (PR) or better, i.e. stringent complete response (sCR), complete response (CR), very good partial response (VGPR) and PR, according to the IMWG criteria.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 4, 2021)

• Assess the safety and tolerability of HDP-101 [ Time Frame: Through study completion, an average of 1 year ]
  Number of patients with serious and non-serious adverse events grouped by system organ class and preferred terms based on Common Terminology Criteria for Adverse Events (CTCAE v 5.0) classification.
• To assess the anticancer activity of HDP-101 in terms of time-to-event (TTE) [ Time Frame: Through study completion, an average of 1 year ]
  Clinical efficacy of HDP-101 measured by Progression Free Survival (PFS) and Overall Survival (OS).

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Assess Safety of HDP-101 in Patients With Relapsed Refractory Multiple Myeloma
• Official Title: A Phase 1/2a, First-in-human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of HDP-101 in Patients With Plasma Cell Disorders Including Multiple Myeloma
• Brief Summary: This study will assess the safety, tolerability, pharmacokinetics (PK) and the therapeutic potential of HDP-101 in patients with plasma cell disorders including multiple myeloma.
• Detailed Description: The study will consists of two parts: a Part 1 dose escalation phase and a Part 2a expansion phase for safety, tolerability, PK, PD, and clinical activity testing. The study will enroll subjects with relapsed/refractory MM or other plasma cell disorders expressing BCMA. An adaptive 2-parameter Bayesian logistic regression model (BLRM) for dose-escalation with overdose control will be used in the dose-escalation phase for determination of the MTD or the RP2D. Dose-expansion phase of the study aims to collect preliminary evidence of antitumor activity and to confirm the safety of the HDP-101 as a monotherapy.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Eligible patients will be enrolled and treated with intravenous HDP-101 every 3 weeks.

A Bayesian logistic regression model will be used to guide dose-escalation during Phase 1 and select the best dose for the Phase 2a of the study.

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Multiple Myeloma
• Plasma Cell Disorder

Intervention

Drug: HDP-101

HDP-101 is available as lyophilized white powder for preparation of infusion.

Study Arms

Experimental: HDP-101

Participants will receive HDP-101 intravenously at one dose every 3 weeks (21 day cycle) until disease progression, intolerable toxicity, Investigator's discretion or patient withdrawal.

During the phase 1 tolerability of different dose levels will be evaluated. During the phase 2a dose expansion part the recommended phase 2 dose (RP2D) of HDP-101 will be administered.

Intervention: Drug: HDP-101

• Publications *: Strassz A, Raab MS, Orlowski RZ, Kulke M, Schiedner G, Pahl A. A First in Human Study Planned to Evaluate HDP-101, an Anti-BCMA Amanitin Antibody-Drug Conjugate with a New Payload and a New Mode of Action, in Multiple Myeloma. Blood 2020; 136 (Supplement 1): 34. doi: https://doi.org/10.1182/blood-2020-142285

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 4, 2021): 78
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 2025
• Estimated Primary Completion Date: August 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male or female aged ≥18 years.
• Life expectancy >12 weeks.
• Eastern Cooperative Oncology Group Performance Status (PS) of 0 to 2.
• A confirmed diagnosis of active MM according to the diagnostic criteria established by the International Myeloma Working Group (IMWG).
• Must have undergone SCT or is considered transplant ineligible.
• Must have undergone prior treatments with antimyeloma therapy which must have included an immunomodulatory drug, proteasome inhibitor, and anti-CD38 treatment, alone or in combination. In addition, the patient should either refractory or intolerant to any established standard of care therapy providing a meaningful clinical benefit for the patient assessed by the Investigator.
• Measurable disease as per IMWG criteria.
• Adequate organ system function as defined in protocol.

Exclusion Criteria:

• For patient entering the Phase 2a part only: Prior treatment with any approved or experimental BCMA-targeting modalities are not allowed.
• Known central nervous system involvement.
• Plasma cell leukemia.
• History of congestive heart failure.
• Autologous or allogenic SCT within 12 weeks before the first infusion or is planning for autologous SCT.
• Symptomatic graft versus host disease post allogenic hemopoietic cell transplant within 12 months prior to the first study treatment infusion.
• Radiotherapy within 21 days prior to the first study treatment infusion.
• History of any other malignancy known to be active.
• Known human immunodeficiency virus infection.
• Patients with active infection requiring systemic anti-infective.
• Patients with positive test results for hepatitis B surface antigen or Hepatitis B core antigen.
• Patients with positive test results for hepatitis C virus (HCV) infection.
• Current active liver or biliary disease.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: András Strassz, MD; + 49 6203 1009 0; clinical@hdpharma.com

• Listed Location Countries: Germany, Hungary, Poland, United States

Administrative Information

• NCT Number: NCT04879043
• Other Study ID Numbers: HDP-101-01
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Heidelberg Pharma AG
• Original Responsible Party: Same as current
• Current Study Sponsor: Heidelberg Pharma AG
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Heidelberg Pharma AG
• Verification Date: July 2023